The association between immunosuppression and cancer in both animals and man is well documented. The fact that virtually every species tested has endogenous retroviruses and that at least some retroviruses have an immunosuppression protein leads to the possibility that these endogenous retroviruses may mediate some degree of immunosuppression in their host species. The objectives of this proposal then are to characterize the immunodepressive effects of a retrovirus protein (p15E) on immune cells and to determine if this protein participates in the general immunosuppresive associated oncogenic retrovirus infections. The specific aims are to determine: i) if p15E interferes with cell-to-cell interaction of leukocytes in one-way mixed leukocyte reactions, ii) if p15E alters macrophage functions, iii) the preferential affinity of p15E for subsets of leukocytes and other somatic cells, iv) if other retroviruses have p15E immunosuppressive proteins, v) if a recombinate of feLV and RD114 causes immunosuppression, vi) the effect of p15E on cell physiological parameter such as membrane alterations, cyclic nucleotide levels and cytoskeletal properties, vii) where p15E has to intracellular effect. If it is determined in the animal models tested that p15E exerts immunosuppression which ultimately enhances the pathogenesis of retrovirus infections then these studies can be expanded to look at the possible role of these virus proteins in human disease. Further, by having studied the mechanism of action of p15E or immune cells it may be possible to identify means of blocking and, possibly, reversing this action.